9-benzyl-2-butyl-8-hydroxyadenine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 9-benzyl-2-butyl-8-hydroxyadenine
• 英文别名: 6-amino-9-benzyl-2-butyl-7H-purin-8-one
• 化学式: C₁₆H₁₉N₅O
• 分子量: 297.36
• InChiKey: BIIMSXSKJCHOQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  84.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  戊酸乙酯 在 盐酸 、 乙醇 、 氨 、 溴 、 sodium acetate 、 sodium 、 溶剂黄146 、 三氯氧磷 作用下， 以 乙醇 、 水 为溶剂， 反应 35.0h， 生成 9-benzyl-2-butyl-8-hydroxyadenine
  参考文献：
  名称：

  Synthesis and structure–activity relationships of 2-substituted-8-hydroxyadenine derivatives as orally available interferon inducers without emetic side effects

  摘要：

  Recently we reported the adenine derivatives (2-4) as new interferon (IFN) inducers. In the present study, we conducted a detailed structure and activity relationship study of 4 and its related derivatives on IFN inducing activity. From this study, we found that compound 4 exhibited the most potent IFN inducing activity in vitro with a minimum effective concentration of 0.01 muM, and 4 also showed strong IFN-inducing activity at doses of more than 0.3 mg/kg by oral administration in mice. This potency was 10-fold stronger than that of Imiquimod. Moreover, 4 did not cause emesis in ferrets even at doses as high as 10 mg/kg, whereas. 80% of animals, were emetic when orally administered with the same dose of Imiquimod. These results indicate that compound 4 is superior to Imiquimod with respect to efficacy and safety. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00369-9

文献信息

• Efficient synthesis of 2,9-disubstituted 8-hydroxyadenine derivatives
  作者：Kosaku Hirota、Kazunori Kazaoka、Itaru Niimoto、Hironao Sajiki

  DOI：10.1039/b300557g

  日期：2003.4.14

  An efficient and general method for the synthesis of 2,9-disubstituted 8-hydroxyadenines, which are expected to have various biological activities, was realized. 5-Amino-4-cyano-2-hydroxyimidazoles (1) were prepared from aminomalononitrile and isocyanates as key intermediates. The condensation of 1a with amidines, imidates, guanidine, urea and thioureas afforded 8-hydroxyadenines (2–6) possessing various substituents at the 2-position. Furthermore, selective alkylation of 2-amino- and 2-hydroxyadenines (4 and 6) successively proceeded to give the corresponding 2-alkylamino- and 2-alkoxyadenines (5 and 7), respectively. 2-Alkylthioadenines (15) were prepared by an analogous reaction of 1a with benzoyl isothiocyanate and subsequent S-alkylation. The imidazoles 1 are most useful intermediates for the synthesis of 8-hydroxyadenine derivatives.

  一种高效且通用的方法被实现，用于合成预期具有多种生物活性的2,9-二取代的8-羟基腺苷。5-氨基-4-氰基-2-羟基咪唑（1）是从氨基丙腈和异氰酸酯作为关键中间体制备的。将1a与氨基脲、咪唑、胍、尿素和硫脲缩合，得到在2位具有各种取代基的8-羟基腺苷（2–6）。此外，对2-氨基和2-羟基腺苷（4和6）进行选择性烷基化，顺利实现，分别得到相应的2-烷基氨基和2-烷氧腺苷（5和7）。2-烷基硫腺苷（15）是通过1a与苯甲酰异硫氰酸酯的类似反应以及随后S-烷基化制备的。咪唑类化合物1是合成8-羟基腺苷衍生物最有用的中间体。
• Discovery of 8-Hydroxyadenines as a Novel Type of Interferon Inducer
  作者：Kosaku Hirota、Kazunori Kazaoka、Itaru Niimoto、Hiroshi Kumihara、Hironao Sajiki、Yoshiaki Isobe、Haruo Takaku、Masanori Tobe、Haruhisa Ogita、Tetsuhiro Ogino、Shinji Ichii、Ayumu Kurimoto、Hajime Kawakami

  DOI：10.1021/jm0203581

  日期：2002.12.1

  9-Benzyl-8-hydroxyadenine (6) was found to possess interferon-inducing activity in vitro as a lead compound. Although replacement of the 9-benzyl group of 6 did not improve the activity, the introduction of a substituent such as alkyl, alkylthio, alkylamino, and alkoxy groups into the 2-position of the adenine ring resulted in a remarkable increase in the activity. The 2-alkylthio (30-32), 2-butylamino (41), and 2-butoxy (47) analogues indicated the highest activities by oral administration to mice.
• Synthesis and structure–activity relationships of 2-substituted-8-hydroxyadenine derivatives as orally available interferon inducers without emetic side effects
  作者：Yoshiaki Isobe、Masanori Tobe、Haruhisa Ogita、Ayumu Kurimoto、Tetsuhiro Ogino、Hajime Kawakami、Haruo Takaku、Hironao Sajiki、Kosaku Hirota、Hideya Hayashi

  DOI：10.1016/s0968-0896(03)00369-9

  日期：2003.8

  Recently we reported the adenine derivatives (2-4) as new interferon (IFN) inducers. In the present study, we conducted a detailed structure and activity relationship study of 4 and its related derivatives on IFN inducing activity. From this study, we found that compound 4 exhibited the most potent IFN inducing activity in vitro with a minimum effective concentration of 0.01 muM, and 4 also showed strong IFN-inducing activity at doses of more than 0.3 mg/kg by oral administration in mice. This potency was 10-fold stronger than that of Imiquimod. Moreover, 4 did not cause emesis in ferrets even at doses as high as 10 mg/kg, whereas. 80% of animals, were emetic when orally administered with the same dose of Imiquimod. These results indicate that compound 4 is superior to Imiquimod with respect to efficacy and safety. (C) 2003 Elsevier Ltd. All rights reserved.